The nonhormonal drug fezolinetant was associated with significant improvements in bothersome vasomotor symptoms (VMS) and in depression and anxiety scores as early as 4 weeks after treatment initiation, according to a real-world study presented at The Menopause Society 2026 Annual Meeting in San Diego.

The findings were detailed in a second preliminary analysis of OPTION-VMS, an ongoing, prospective, longitudinal, multicenter phase 4 US study involving women aged 40-75 years. Women in the study were prescribed fezolinetant, selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI), or other nonhormonal therapies for bothersome VMS.

The March 2026 data analysis included 993 enrolled women, of whom 859 completed the Menopause-Specific Quality of Life Questionnaire (MENQOL) at baseline and at least one follow-up visit. Astellas Pharma Inc., which makes fezolinetant (Veozah), funded the study.

Among fezolinetant users, the vast majority (93%) had moderate-to-severe VMS, and 86% were postmenopausal. Overall, 56% of participants were White and 38% were Black or African American; 31% had hypertension, 21% had hyperlipidemia, 17% had depression, and 15% had anxiety.

The primary endpoint was change in VMS. Among fezolinetant users, the MENQOL VMS domain score improved significantly by week 12 (least-squares mean change from baseline, -2.66; 95% CI, -2.95 to -2.37; P < .001) and as early as week 4.

“Fezolinetant is a specific ‘bullet’ directed at the source of the hot flashes,” said Nanette Santoro, MD, the E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado School of Medicine in Aurora and an author of the study. “While the NK [neurokinin]-based therapies are fairly new, they seem to have very high effectiveness, and do not have off-target side effects. Patients really appreciate that.”

In the study, the 375 patients who started fezolinetant showed significant improvements in depressive and anxiety symptoms at week 12, with a change from baseline of -3.04 on the Patient Health Questionnaire-9 for depression (95% CI, -3.63 to -2.45; P < .001) and -2.44 on the Generalized Anxiety Disorder-7 scale for anxiety (95% CI, -3.00 to -1.89; P < .001). Lower scores indicate improvement. Depression and anxiety were exploratory endpoints.

“It’s exciting to see that in the phase 4 real-world data that they’re finding not only does it reduce hot flashes, which was the primary indication, but that we’re also seeing a signal for reduction in depression and anxiety symptoms,” said Erin Duralde, MD, MPH, MSCP, One Medical’s national director of women’s health and menopause program leader.

Although it was not a comparative study, it also evaluated the effectiveness of traditional antidepressants (SSRI or SNRI) and other nonhormonal therapies, such as gabapentin and oxybutynin. These therapies also showed significant improvements in depression and anxiety at weeks 4, 8, and 12.

Among the 358 patients who received an SSRI or SNRI, the mean change at week 12 was -2.60 for depression (95% CI, -3.21 to -1.98) and -2.41 for anxiety (95% CI, -2.99 to -1.84; P < .001 for both). The 126 patients who received other nonhormonal therapies saw a least-squares mean change at week 12 of -1.94 for depression (95% CI, -2.81 to -1.06) and -1.79 for anxiety (95% CI, -2.59 to -0.98; both P < .001).

“What is also interesting and important is that the depressive symptoms improve most dramatically by week 4,” Santoro said. This is different from what is expected when treating major depression, for example, where patients are often required to wait as long as 6 weeks or more to feel improvements, she said.

Two patients experienced hepatic laboratory test abnormalities, but overall, the rate of drug-related adverse events was infrequent with fezolinetant, researchers said. The abstract reported no drug-related serious treatment-emergent adverse events or hepatotoxicity.

The FDA added a boxed warning to the drug because of the risk for rare but serious liver injury, meaning patients taking the medication need to be monitored periodically for liver function.

“Because it is a new medication, the long-term risks cannot be known at this time,” Santoro said. “Short-term risks are concerns about possible liver toxicity, and patients are carefully monitored for this possibility, which seems so far to be very rare.”

The study was funded by Astellas Pharma. Santoro reported being a member of the scientific advisory board for Astellas, Bayer, Novo Nordisk, Eli Lilly and Company, Perrigo, and MenoGeniX. Duralde reported being employed by One Medical and having no other relevant financial relationships.

Sony Salzman is an Emmy Award-winning journalist covering science and medicine with bylines in The Atlantic, STAT News, NBC, MedPage Today, and The Boston Globe. Previously, she worked as the coordinating producer of ABC’s Medical Unit.